tbuckley/cabot-search huggingface dataset:
Combination Dabrafenib and Trametinib Versus Combination Nivolumab and Ipilimumab for Patients With Advanced <i>BRAF</i>-Mutant Melanoma: The DREAMseq Trial—ECOG-ACRIN EA6134
Authors: Michael B. Atkins, Sandra J. Lee, Bartosz Chmielowski, Ahmad A. Tarhini, Gary I. Cohen, Thach-Giao Truong, Helen H. Moon, Diwakar Davar, Mark O'Rourke, Joseph J. Stephenson, Brendan D. Curti, Walter J. Urba, Joanna M. Brell, Pauline Funchain, Kari L. Kendra, Alexandra P. Ikeguchi, Anthony Jaslowski, Charles L. Bane, Mark A. Taylor, Madhuri Bajaj, Robert M. Conry, Robert J. Ellis, Theodore F. Logan, Noel Laudi, Jeffrey A. Sosman, David G. Crockett, Andrew L. Pecora, Ian J. Okazaki, Sowjanya Reganti, Sunandana Chandra, Samantha Guild, Helen X. Chen, Howard Z. Streicher, Jedd D. Wolchok, Antoni Ribas, John M. Kirkwood
Journal: Journal of Clinical Oncology (2022)

Combination programmed cell death protein 1/cytotoxic T-cell lymphocyte-4-blockade and dual BRAF/MEK inhibition have each shown significant clinical benefit in patients with
Understanding Modern Medical Centers: Beyond Simone—Intersectional Maxims for a New Era
Authors: Stephanie L. Graff, Tanya Wildes, Narjust Duma, Don S. Dizon, Noelle K. LoConte, Edith Mitchell, Martina C. Murphy, Edith A. Perez, Sarah M. Temkin, Pamela L. Kunz, Karen M. Winkfield
Journal: Journal of Clinical Oncology (2022)
Associations of Symptom Clusters and Health Outcomes in Adult Survivors of Childhood Cancer: A Report From the St Jude Lifetime Cohort Study
Authors: Hyewon Shin, William N. Dudley, Nickhill Bhakta, Madeline R. Horan, Zhaoming Wang, T. Robin Bartlett, Deokumar Srivastava, Yutaka Yasui, Justin N. Baker, Leslie L. Robison, Kirsten K. Ness, Kevin R. Krull, Melissa M. Hudson, I-Chan Huang
Journal: Journal of Clinical Oncology (2022)

To identify symptom clusters among adult survivors of childhood cancers and test associations with health-related quality of life (HRQOL) and physical and neurocognitive performance.
<i>Mudras</i> in Medicine: A Role for Dance in Appreciating Nonverbal Communication in the Clinical Encounter
Authors: Maheetha Bharadwaj, Dipal Nagda, Lipika Goyal
Journal: Journal of Clinical Oncology (2022)

We present a classical Indian dance piece that depicts a patient and their partner receiving a cancer diagnosis from their oncologist.The primary purpose of this piece was to provide a vehicle for patients, physicians, and caregivers to process a life-altering cancer diagnosis.The piece was choreographed and performed by two of the authors (M.B. and D..), who are medical students and classically trained Bharatanatyam dancers, and the project was guided under the mentorship of the senior author (L.G.) who is a medical oncologist.Through the process of designing this project during the COVID-19 pandemic, the authors also reflect on the role of visual arts in providing a space for contemplation and in promoting nonverbal communication in the era of virtual medicine.
Most black people in UK face discrimination from healthcare staff, survey finds
Authors: Gareth Iacobucci
Journal: BMJ (2022)

Most black people in UK face discrimination from healthcare staff, survey finds Gareth IacobucciMost black people living in the UK have experienced prejudice from healthcare professionals because of their ethnicity, with younger people feeling especially discriminated against, a survey has revealed. 1 Almost two thirds (65%) of black people who responded to a survey said that they had experienced prejudice from doctors and other staff in healthcare settings.This rose to three quarters (75%) among black people aged 18 to 34. 1
Allogeneic stem cell transplantation compared to conservative management in adults with inborn errors of immunity
Authors: Morgane Cheminant, Thomas A. Fox, Mickael Alligon, Olivier Bouaziz, Bénédicte Neven, Despina Moshous, Stéphane Blanche, Aurélien Guffroy, Claire Fieschi, Marion Malphettes, Nicolas Schleinitz, Antoinette Perlat, Jean-François Viallard, Nathalie Dhedin, Françoise Sarrot-Reynauld, Isabelle Durieu, Sébastien Humbert, Fanny Fouyssac, Vincent Barlogis, Benjamin Carpenter, Rachael Hough, Arian Laurence, Ambroise Marçais, Ronjon Chakraverty, Olivier Hermine, Alain Fischer, Siobhan O. Burns, Nizar Mahlaoui, Emma C. Morris, Felipe Suarez
Journal: Blood (2022)
Safety data needed for concurrent use of ARV-based PrEP
Authors: Megan S Dunbar, Jessica Rodrigues, Manju Chatani, Jared M Baeten, Craig W Hendrix, Thesla Palanee-Phillips, Ariane van der Straten, Nyaradzo Mgodi, Elizabeth Brown, Cleopatra Makura, Shakirah Namwanje, Kristine Torjesen
Journal: The Lancet HIV (2022)
Pandemic preparedness and response: exploring the role of universal health coverage within the global health security architecture
Authors: Arush Lal, Salma M Abdalla, Vijay Kumar Chattu, Ngozi Adaeze Erondu, Tsung-Ling Lee, Sudhvir Singh, Hala Abou-Taleb, Jeanette Vega Morales, Alexandra Phelan
Journal: The Lancet Global Health (2022)

In response to the COVID-19 pandemic, several international initiatives have been developed to strengthen and reform the global architecture for pandemic preparedness and response, including proposals for a pandemic treaty, a Pandemic Fund, and mechanisms for equitable access to medical countermeasures. These initiatives seek to make use of crucial lessons gleaned from the ongoing pandemic by addressing gaps in health security and traditional public health functions. However, there has been insufficient consideration of the vital role of universal health coverage in sustainably mitigating outbreaks, and the importance of robust primary health care in equitably and efficiently safeguarding communities from future health threats. The international community should not repeat the mistakes of past health security efforts that ultimately contributed to the rapid spread of the COVID-19 pandemic and disproportionately affected vulnerable and marginalised populations, especially by overlooking the importance of coherent, multisectoral health systems. This Health Policy paper outlines major (although often neglected) gaps in pandemic preparedness and response, which are applicable to broader health emergency preparedness and response efforts, and identifies opportunities to reconceptualise health security by scaling up universal health coverage. We then offer a comprehensive set of recommendations to help inform the development of key pandemic preparedness and response proposals across three themes—governance, financing, and supporting initiatives. By identifying approaches that simultaneously strengthen health systems through global health security and universal health coverage, we aim to provide tangible solutions that equitably meet the needs of all communities while ensuring resilience to future pandemic threats.
Independent and joint associations of weightlifting and aerobic activity with all-cause, cardiovascular disease and cancer mortality in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial
Authors: Jessica Gorzelitz, Britton Trabert, Hormuzd A Katki, Steven C Moore, Eleanor L Watts, Charles E Matthews
Journal: British Journal of Sports Medicine (2022)

Objectives Both aerobic moderate to vigorous physical activity (MVPA) and muscle-strengthening exercise (MSE) are recommended, but the mortality benefits of weightlifting, a specific type of MSE, are limited. Methods In the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, we used Cox proportional hazards regression to calculate hazard ratios (HRs) and 95% CIs for the associations between weightlifting and mortality, adjusting for demographics, lifestyle and behavioural risk factors. The sample included 99 713 adults who completed the follow-up questionnaire that assessed weightlifting who were subsequently followed up through 2016 to determine mortality (median 9, IQR 7.6–10.6 years). Results Mean age at the follow-up questionnaire was 71.3 (IQR 66–76) years, 52.6% female, with mean body mass index of 27.8 (SD 4.9) kg/m 2 . Weightlifting was associated with a 9% lower risk of all-cause mortality (HR=0.91 (95% CI 0.88 to 0.94)) and CVD mortality (0.91 (95% CI 0.86 to 0.97)) after adjusting for MVPA. Joint models revealed that adults who met aerobic MVPA recommendations but did not weightlift had a 32% lower all-cause mortality risk (HR=0.68 (95% CI 0.65 to 0.70)), while those who also reported weightlifting 1–2 times/week had a 41% lower risk (HR=0.59 (95% CI 0.54 to 0.64)), both compared with adults reporting no aerobic MVPA or weightlifting. Without adjustment for MVPA, weightlifting was associated with lower cancer mortality (HR=0.85 (95% CI 0.80 to 0.91)). Conclusion Weightlifting and MVPA were associated with a lower risk of all-cause and CVD mortality, but not cancer mortality. Adults who met recommended amounts of both types of exercise appeared to gain additional benefit.
Interferon-γ induces immunosuppression in salivary adenoid cystic carcinoma by regulating programmed death ligand 1 secretion
Authors: Qiuyun Fu, Xingchi Liu, Houfu Xia, Yicun Li, Zili Yu, Bing Liu, Xuepeng Xiong, Gang Chen
Journal: International Journal of Oral Science (2022)

Abstract Interferon-γ (IFN-γ), a key effector molecule in anti-tumor immune response, has been well documented to correlate with the intratumoral infiltration of immune cells. Of interest, however, a high level of IFN-γ has been reported in salivary adenoid cystic carcinoma (SACC), which is actually a type of immunologically cold cancer with few infiltrated immune cells. Investigating the functional significance of IFN-γ in SACC would help to explain such a paradoxical phenomenon. In the present study, we revealed that, compared to oral squamous cell carcinoma cells (a type of immunologically hot cancer), SACC cells were less sensitive to the growth-inhibition effect of IFN-γ. Moreover, the migration and invasion abilities of SACC cells were obviously enhanced upon IFN-γ treatment. In addition, our results revealed that exposure to IFN-γ significantly up-regulated the level of programmed death ligand 1 (PD-L1) on SACC cell-derived small extracellular vesicles (sEVs), which subsequently induced the apoptosis of CD8 + T cells through antagonizing PD-1. Importantly, it was also found that SACC patients with higher levels of plasma IFN-γ also had higher levels of circulating sEVs that carried PD-L1 on their surface. Our study unveils a mechanism that IFN-γ induces immunosuppression in SACC via sEV PD-L1, which would account for the scarce immune cell infiltration and insensitivity to immunotherapy.
Preparing for the next pandemic: reserve laboratory staff are crucial
Authors: Jordan P Skittrall, Neil Bentley, Tim Wreghitt, Paul Silverston, Huina Yang, Sani H Aliyu, Anna A Smielewska
Journal: BMJ (2022)

UK laboratories conducted over 200 million SARS-CoV-2 polymerase chain reaction tests between January 2020 and April 2022. 1 Laboratory tests were used to diagnose disease, to inform public health actions such as isolation, and to reduce spread through testing asymptomatic people. 2 -4 The rate of laboratory testing in the UK expanded rapidly at the start of 2020, from 100 tests a day on 4 January 2020, to 10 000/day on 23 March, to 100 000/day on 9 July. 1 Although these numbers are substantial, demand for testing at that time exceeded availability, and only those meeting a strict set of criteria were tested.Despite government pledges to provide 100 000 tests per day by May 2020 as part of the UK test and trace scheme, 5 6 demand quickly outstripped capacity to set up testing safely in new laboratories, conduct quality assurance of the tests, and process samples.In short, surge capacity was already required by the time the first tests were available. 7Availability of laboratory facilities and resources-from basic reagents to IT support-was a substantial challenge, 8 9 but aside from the distribution of positive control material (which was quickly solved) the biggest bottleneck was finding trained staff to carry out the tests. 10 11Maintaining surplus laboratory capacity for emergencies is expensive, and therefore politically and economically unpalatable.Nevertheless, covid-19 has shown that effective surge capacity is a vital part of pandemic preparedness.
Primary cardioprotection with dexrazoxane in patients with childhood cancer who are expected to receive anthracyclines: recommendations from the International Late Effects of Childhood Cancer Guideline Harmonization Group
Authors: Esmée C de Baat, Elvira C van Dalen, Renée L Mulder, Melissa M Hudson, Matthew J Ehrhardt, Frederike K Engels, Elizabeth A M Feijen, Heynric B Grotenhuis, Jan M Leerink, Livia Kapusta, Gertjan J L Kaspers, Remy Merkx, Luc Mertens, Roderick Skinner, Wim J E Tissing, Florent de Vathaire, Paul C Nathan, Leontien C M Kremer, Annelies M C Mavinkurve-Groothuis, Saro Armenian
Journal: The Lancet Child & Adolescent Health (2022)
Supramolecular hybrid hydrogels as rapidly on-demand dissoluble, self-healing, and biocompatible burn dressings
Authors: A. Aslihan Gokaltun, Letao Fan, Luca Mazzaferro, Delaney Byrne, Martin L. Yarmush, Tianhong Dai, Ayse Asatekin, O. Berk Usta
Journal: Bioactive Materials (2022)

Despite decades of efforts, state-of-the-art synthetic burn dressings to treat partial-thickness burns are still far from ideal. Current dressings adhere to the wound and necessitate debridement. This work describes the first "supramolecular hybrid hydrogel (SHH)" burn dressing that is biocompatible, self-healable, and on-demand dissoluble for easy and trauma-free removal, prepared by a simple, fast, and scalable method. These SHHs leverage the interactions of a custom-designed cationic copolymer via host-guest chemistry with cucurbit[7]uril and electrostatic interactions with clay nanosheets coated with an anionic polymer to achieve enhanced mechanical properties and fast on-demand dissolution. The SHHs show high mechanical strength (>50 kPa), self-heal rapidly in ∼1 min, and dissolve quickly (4-6 min) using an amantadine hydrochloride (AH) solution that breaks the supramolecular interactions in the SHHs. Neither the SHHs nor the AH solution has any adverse effects on human dermal fibroblasts or epidermal keratinocytes
Dietary fats and prevention of cardiovascular disease
Authors: J. Mann, M. Skeaff, S. Truswell, F. B Hu, F. Sacks, W. C Willett, L. Hooper, C. D Summerbell, R. L Thompson, N. E Capps, G. D. Smith, R. A Riemersma, S. Ebrahim
Journal: BMJ (2001)
Advancing Nitinol: From heat treatment to surface functionalization for nickel–titanium (NiTi) instruments in endodontics
Authors: Wai-Sze Chan, Karan Gulati, Ove A. Peters
Journal: Bioactive Materials (2022)

Nickel-titanium (NiTi) alloy has been extensively researched in endodontics, particularly in cleaning and shaping the root canal system. Research advances have primarily focused on the design, shape, and geometry of the NiTi files as well as metallurgy and mechanical properties. So far, extensive investigations have been made surrounding surface and thermomechanical treatments, however, limited work has been done in the realm of surface functionalization to augment its performance in endodontics. This review summarizes the unique characteristics, current use, and latest developments in thermomechanically treated NiTi endodontic files. It discusses recent improvements in nano-engineering and the possibility of customizing the NiTi file surface for added functionalization. Whilst clinical translation of this technology has yet to be fully realized, future research direction will lie in the use of nanotechnology.
The differential effects of sleep deprivation on pain perception in individuals with or without chronic pain: A systematic review and meta-analysis
Authors: Jeremy R. Chang, Siu-Ngor Fu, Xun Li, Shirley X. Li, Xiaoyue Wang, Zhixing Zhou, Sabina M. Pinto, Dino Samartzis, Jaro Karppinen, Arnold YL. Wong
Journal: Sleep Medicine Reviews (2022)
Biomimetic cell membrane-coated glucose/oxygen-exhausting nanoreactor for remodeling tumor microenvironment in targeted hypoxic tumor therapy
Authors: Haoyu Guo, Weiyue Zhang, Lutong Wang, Zengwu Shao, Xin Huang
Journal: Biomaterials (2022)

Hypoxia is a common feature within many types of solid tumors, which is closely associated with limited efficacy for tumor therapies. Moreover, the inability to reach hypoxic tumor cells that are distant from blood vessels results in tumor-targeting and penetrating drug delivery systems in urgent need. Here, glucose oxidase (GOX) and hypoxia-activated prodrug tirapazamine (TPZ) are loaded into photothermal conversion agent polydopamine (PDA) as the glucose/oxygen-exhausting nanoreactor named PGT. We further construct a tumor cell membrane-coated nanovesicle for the targeted delivery of PGT. This biomimetic nanovesicle exhibits significantly improved tumor-targeting and tumor-penetrating abilities. After internalization by the tumor cells, the loaded drug is quickly released in response to near-infrared (NIR) laser. The PGT nanoreactor can exhaust glucose and oxygen, and further enhance hypoxia within tumor, which efficiently inhibits hypoxic tumor by combining starvation therapy and hypoxia-activated chemotherapy. Mechanically, it is revealed that the nanoreactor significantly increases hypoxia level and downregulates the expression of hypoxia-inhibitory factor-1α (HIF-1α), thereby promoting T cell activation and macrophage polarization to remodel tumor immunosuppressive microenvironment. Therefore, this tumor microenvironment-regulable nanoreactor with sustainable and cascade targeted starvation-chemotherapy provides a novel insight into the treatment of hypoxic tumor.
Functional immune responses against SARS-CoV-2 variants of concern after fourth COVID-19 vaccine dose or infection in patients with blood cancer
Authors: Annika Fendler, Scott T.C. Shepherd, Lewis Au, Mary Wu, Ruth Harvey, Katalin A. Wilkinson, Andreas M. Schmitt, Zayd Tippu, Benjamin Shum, Sheima Farag, Aljosja Rogiers, Eleanor Carlyle, Kim Edmonds, Lyra Del Rosario, Karla Lingard, Mary Mangwende, Lucy Holt, Hamid Ahmod, Justine Korteweg, Tara Foley, Taja Barber, Andrea Emslie-Henry, Niamh Caulfield-Lynch, Fiona Byrne, Daqi Deng, Svend Kjaer, Ok-Ryul Song, Christophe J. Queval, Caitlin Kavanagh, Emma C. Wall, Edward J. Carr, Simon Caidan, Mike Gavrielides, James I. MacRae, Gavin Kelly, Kema Peat, Denise Kelly, Aida Murra, Kayleigh Kelly, Molly O’Flaherty, Robyn L. Shea, Gail Gardner, Darren Murray, Sanjay Popat, Nadia Yousaf, Shaman Jhanji, Kate Tatham, David Cunningham, Nicholas Van As, Kate Young, Andrew J.S. Furness, Lisa Pickering, Rupert Beale, Charles Swanton, Sonia Gandhi, Steve Gamblin, David L.V. Bauer, George Kassiotis, Michael Howell, Emma Nicholson, Susanna Walker, Robert J. Wilkinson, James Larkin, Samra Turajlic
Journal: Cell Reports Medicine (2022)

Patients with blood cancer continue to have a greater risk of inadequate immune responses following three COVID-19 vaccine doses and risk of severe COVID-19 disease. In the context of the CAPTURE study (NCT03226886), we report immune responses in 80 patients with blood cancer who received a fourth dose of BNT162b2. We measured neutralizing antibody titers (NAbTs) using a live virus microneutralization assay against wild-type (WT), Delta, and Omicron BA.1 and BA.2 and T cell responses against WT and Omicron BA.1 using an activation-induced marker (AIM) assay. The proportion of patients with detectable NAb titers and T cell responses after the fourth vaccine dose increased compared with that after the third vaccine dose. Patients who received B cell-depleting therapies within the 12 months before vaccination have the greatest risk of not having detectable NAbT. In addition, we report immune responses in 57 patients with breakthrough infections after vaccination.
Cardiovascular baroreflex circuit moonlights in sleep control
Authors: Yuanyuan Yao, Zeke Barger, Mohammad Saffari Doost, Chak Foon Tso, Dana Darmohray, Daniel Silverman, Danqian Liu, Chenyan Ma, Ali Cetin, Shenqin Yao, Hongkui Zeng, Yang Dan
Journal: Neuron (2022)

Sleep disturbances are strongly associated with cardiovascular diseases. Baroreflex, a basic cardiovascular regulation mechanism, is modulated by sleep-wake states. Here, we show that neurons at key stages of baroreflex pathways also promote sleep. Using activity-dependent genetic labeling, we tagged neurons in the nucleus of the solitary tract (NST) activated by blood pressure elevation and confirmed their barosensitivity with optrode recording and calcium imaging. Chemogenetic or optogenetic activation of these neurons promoted non-REM sleep in addition to decreasing blood pressure and heart rate. GABAergic neurons in the caudal ventrolateral medulla (CVLM)-a downstream target of the NST for vasomotor baroreflex-also promote non-REM sleep, partly by inhibiting the sympathoexcitatory and wake-promoting adrenergic neurons in the rostral ventrolateral medulla (RVLM). Cholinergic neurons in the nucleus ambiguous-a target of the NST for cardiac baroreflex-promoted non-REM sleep as well. Thus, key components of the cardiovascular baroreflex circuit are also integral to sleep-wake brain-state regulation.
A microphysiological system-based potency bioassay for the functional quality assessment of mesenchymal stromal cells targeting vasculogenesis
Authors: Johnny Lam, Byungjun Lee, James Yu, Brian J. Kwee, Yangji Kim, Jiho Kim, Yeongmin Choi, Jun Sung Yoon, Youngsoo Kim, Kyusuk Baek, Noo Li Jeon, Kyung E. Sung
Journal: Biomaterials (2022)

Mesenchymal stromal cells (MSCs) continue to be proposed for use in clinical trials to treat various diseases due to their therapeutic potential to pleiotropically influence endogenous regenerative processes, such as vasculogenesis. However, the functional heterogeneity of MSCs has hampered their clinical success and poses a significant manufacturing challenge with respect to MSC quality control. Here, we evaluated and qualified a quantitative bioassay based on an enhanced-throughput, microphysiological system to measure the specific paracrine bioactivity of MSCs to stimulate vasculogenesis as a measure of MSC potency. Using this novel bioassay, MSCs derived from multiple donors at different passages were co-cultured with human umbilical vein endothelial cells (HUVECs) and exhibited significant heterogeneity in vasculogenic potency between donors and cell passage. Using our microphysiological system (MPS)-based platform, we demonstrated that variations in MSC vasculogenic bioactivity were maintained when assayed across laboratories and operators. The differences in MSC vasculogenic bioactivity were also correlated with the baseline expression of several genes involved in vasculogenesis (hepatocyte growth factor (HGF), angiopoietin-1 (ANGPT)) or the production of matricellular proteins (fibronectin (FN), insulin-like growth factor-binding protein 7 (IGFBP7)). These findings emphasize the significant functional heterogeneity of MSCs in vasculogenic bioactivity and suggest that changes in baseline gene expression of vasculogenic or matricellular protein genes during manufacturing may affect this bioactivity. The development of a reliable and functionally relevant potency assay for measuring the specific vasculogenic bioactivity of manufactured MSCs will help to reliably assure their quality when used in appropriate clinical trials.